Lean NASH: distinctiveness and clinical implication

Area of Science:

• Hepatology
• Metabolic Diseases
• Internal Medicine

Background:

• Non-alcoholic fatty liver (NAFL) in lean individuals, termed 'lean NASH,' shares links with metabolic syndrome (MS) and insulin resistance (IR).
• Hallmarks include subtle alterations in body and regional adiposity not exceeding standard obesity cut-offs.
• Lean NASH is a variant phenotype of non-alcoholic steatohepatitis (NASH) metabolically resembling 'metabolically obese normal weight' (MONW) individuals.

Purpose of the Study:

• To review and analyze existing literature on the pathogenesis of NASH in lean or non-obese individuals.
• To highlight the pathophysiological relevance of fat distribution in characterizing 'lean NASH'.

Main Methods:

• Systematic review and critical analysis of English-language literature on NASH in lean/non-obese individuals.
• Focus on pathogenesis and metabolic similarities to MONW.

Main Results:

• 'Lean NASH' detection in non-obese individuals (by BMI and waist circumference) suggests NASH subsets with ectopic fat not identified by standard metrics.
• Visceral and deep subcutaneous adipose tissue volume and behavior are crucial in non-obese subjects.
• Genetic predisposition, environmental factors (nutrition, diet, gut microbiome) may play a role in pathogenesis.

Conclusions:

• Nomenclature challenges exist due to clinical dissimilarities despite biological similarities in related syndromes.
• "Lean NASH" provides a framework for refining understanding of this fatty liver subset in non-obese populations.
• Further research is needed for a universally accepted pathophysiological or etiological classification.